TAK1 Is a Key Regulator of Oncogenic Signaling and Differentiation Blockade in Rhabdomyosarcoma

Authors

• Anh Tuan Vuong
• Aniket S Joshi
• Anirban Roy
• Kavya Mathukumalli
• Phuong T Ho
• Raksha Bhat
• Meiricris Tomaz da Silva
• Tagari Samanta
• Meghana V Trivedi
• Bin Guo
• Benny A Kaipparettu
• Ashok Kumar

Language

English

Publication Date

5-1-2026

Journal

Oncogene

DOI

10.1038/s41388-026-03767-z

PMID

41942630

PMCID

PMC13136027

PubMedCentral® Posted Date

4-6-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma with a skeletal muscle phenotype, accounting for approximately 50% of all pediatric soft tissue sarcomas and 8% of all childhood cancers. Although RMS cells express myogenic regulatory factors, they fail to undergo terminal differentiation into mature muscle cells. Transforming growth factor β-activated kinase 1 (TAK1) is a key signaling mediator that activates multiple intracellular pathways, yet its role in RMS has remained unknown. Here, we show that TAK1 expression and activity are markedly elevated in RMS cell lines and patient tumor specimens. RNA-Seq and reverse phase protein array (RPPA) analyses revealed that TAK1 regulates the expression and activity of many molecules involved in cell cycle control, cell proliferation, and oncogenic signaling. Inhibition of TAK1 suppresses RMS cell proliferation, migration, and invasiveness, while also promoting terminal myogenic differentiation. TAK1 inhibits differentiation in RMS, in part, through up-regulating YAP1 signaling. Our results also demonstrate that inducible knockdown of TAK1 in human RMS xenografts retards tumor growth and enhances myogenic differentiation in vivo. Collectively, these findings uncover a previously unrecognized role for TAK1 in RMS growth and differentiation, and suggest that TAK1 can be a potential therapeutic target for the treatment of RMS.

Keywords

Humans, Rhabdomyosarcoma, MAP Kinase Kinase Kinase 7, MAP Kinase Kinase Kinases, Animals, Signal Transduction, Cell Differentiation, Cell Line, Tumor, YAP-Signaling Proteins, Cell Proliferation, Mice, Adaptor Proteins, Signal Transducing, Cell Movement, Transcription Factors, Gene Expression Regulation, Neoplastic, Phosphoproteins

Published Open-Access

yes

Recommended Citation

Vuong, Anh Tuan; Joshi, Aniket S; Roy, Anirban; et al., "TAK1 Is a Key Regulator of Oncogenic Signaling and Differentiation Blockade in Rhabdomyosarcoma" (2026). Faculty, Staff and Students Publications. 8105.
https://digitalcommons.library.tmc.edu/baylor_docs/8105